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ImmunoPath > Immune modulating therapies 1 > Flashcards

Immune modulating therapies 1 Flashcards

1
Q
  1. What are the two ways in which B cells can undergo clonal expansion once activated?
A

They can differentiate into T-cell independent IgM plasma cells
They can undergo a germinal centre reaction (with help from T helper cells) and become IgG memory and plasma cells

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2
Q
  1. Which type of T cell undergoes a more pronounced proliferation following activation?
A

CD8 > CD4

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3
Q
  1. List three types of antigen-presenting cell.
A

Dendritic cells
Macrophages
B lymphocytes

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4
Q
  1. Which cell surface receptor is used in the influenza vaccine?
A

Haemagglutinin (HA) – this is a receptor-binding and membrane fusion glycoprotein

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5
Q
  1. Describe how haemagglutinin inhibition assays work.
A

If you put normal red blood cells in a petri dish, they will clump at the bottom forming a red spot
If you add influenza virus, the HA makes red cells stick together and causes a diffuse coloration across the well
If you add the serum of someone who has a lot of antibodies against HA, it will inhibit the haemagglutination effects of HA so the red cells remain as a discrete red spot
The higher the dilution of serum at which the red cells remain as a little dot, the more antibodies are present in the serum
NOTE: sialic acid receptors on RBCs bind to HA leading to haemagglutination

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6
Q
  1. How long does protection from the influenza vaccine last?
A

Starts 7 days after the vaccine and protection lasts for 6 months

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7
Q
  1. What agent is used in the BCG vaccine?
A

Attenuated strain of Mycobacterium bovis

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8
Q
  1. Describe the protection that is achieved by using the BCG.
A

Some protection against primary infection

Mainly protects against progression to active TB

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9
Q
  1. What is a live attenuated virus vaccine? List some examples.
A

The organism is alive but modified to limit its pathogenesis
Examples: MMR, typhoid, BCG, yellow fever, polio (Sabin)

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10
Q
  1. List some advantages and disadvantages of live attenuated virus vaccines.
A

Advantages: establishes infections, raises broad immune response against multiple antigens, activates all phases of the immune system, often confer life-long immunity after one dose
Disadvantages: storage problems, possible reversion to virulence, spread to contacts, cannot be used in immunocompromised patients

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11
Q
  1. List some examples of the following types of vaccine:
    a. Toxoids
    b. Component/Subunit
A 
a.	Toxoids
Diphtheria
Tetanus
b.	Component/Subunit 
Hep B (HBsAg)
HPV (capsid)
Influenza (HA)
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12
Q
  1. What are the advantages and disadvantages of inactivated/component vaccines?
A

Advantages – no mutation or reversion, can be used in immunodeficient patients, easier storage, lower cost
Disadvantages – often do not follow normal route of infection, poor immunogenicity, may need multiple injections, may require conjugates/adjuvants

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13
Q
  1. Describe how conjugate vaccines work.
A

Polysaccharide and protein carrier
Polysaccharide induces a T-cell independent B cell response (transient)
Addition of the protein carrier promoted T cell immunity which enhances B cell/antibody responses

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14
Q
  1. List some examples of conjugate vaccines.
A

Haemophilus influenzae type B
Meningococcus
Pneumococcus

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15
Q
  1. Describe how adjuvants work.
A

Increases the immune response without altering its specificity
They mimic the action of PAMPs on TLR and other PRRs

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16
Q
  1. List some examples of adjuvants.
A 
Aluminium salts (MOST COMMON)
Lipids (monophosphoryl lipid A)
17
Q
  1. What are dendritic cell vaccines?
A

Used against tumours
You collect some dendritic cells from the patient and load them with the antigen from the tumour to try and boost the immune response against tumour antigens

18
Q
  1. What are the main indications for haematopoietic stem cell transplantation?
A

Life-threatening immunodeficiency (SCID)

Haematological malignancy

19
Q
  1. List some indications for IVIG.
A 
Primary antibody defect 
•	X-linked agammaglobulinaemia
•	X-linked hyper IgM syndrome 
•	Common variable immunodeficiency
Secondary antibody defect
•	CLL
•	Multiple myeloma 
•	After bone marrow transplantation
20
Q
  1. When might specific immunoglobulin be given?
A

Passive immunity as post-exposure prophylaxis (e.g. Hep B, tetanus, rabies, VZIG)

21
Q
  1. List four types of T cell adoptive cell transfer.
A

Virus-specific T cells
Tumour infiltrating T cells (TIL)
T cell receptor T cells (TCR)
Chimeric antigen receptor T cells (CAR T Cell Therapy)

22
Q
  1. Using an example, describe how virus-specific T cells are used.
A

Used for EBV in patients who are immunosuppressed to prevent the development of lymphoproliferative disease
Blood is taken from the patient or from a donor
Peripheral blood mononuclear cells are isolated and stimulated with EBV peptides
This creates an expansion of EBV-specific T cells which are then reinfused into the patient

23
Q
  1. Describe how TCR and CAR T cell therapy works.
A

T cells are taken from the patient and vectors are used to insert gene fragments that encode receptors
In TCR therapy, the gene will encode a specific TCR (e.g. against tumour antigen)
In CAR therapy, the receptors are chimeric (containing both B and T cell components)

24
Q
  1. Describe a use of CAR T cell therapy.
A

Used to target CD19 (present on B cells)
Receptors on the CAR cell have an immunoglobulin variable domain and is joined to a TCR
This means that it recognises CD19 through an immunoglobulin domain but signals through the TCR pathway
used in ALL and NHL

25
Q
  1. What is ipilimumab and how does it work?
A

CTLA4 and CD28 are both expressed by T cells and they recognise antigens (CD80 and CD86) on APCs
Signalling through CD28 results in a stimulatory response of T cells
Signalling through CTLA4 results in an inhibitory response of T cells
Ipilimumab is a monoclonal antibody that blocks CTLA4 thereby removing this inhibitory response
It is used in advanced melanoma

26
Q
  1. Explain the use of antibodies against PD-1 in treating cancer.
A

PD-1 and PD-2 ligands are present on APCs and interact via PD-1 receptors on T cells to cause an inhibitory response
They can also be expressed by some tumour cells
Pembrolizumab and nivolumab are antibodies that are specific to PD-1, thereby blocking this effect
This is also used in advanced melanoma

27
Q
  1. List some examples of the therapeutic use of recombinant cytokines.
A

Interferon alpha – used as an adjunct in the treatment of Hep B, Hep C, Kaposi sarcoma, CML and multiple myeloma

Interferon beta – Behcet’s disease, relapsing MS

Interferon gamma – chronic granulomatous disease

ImmunoPath (9 decks)

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